Project Summary Despite recent advances, infectious diseases still account for 50% of years of life lost in sub-Saharan Africa. There has been growing international agreement that a critical roadblock to controlling this epidemic and endemic health burden has been the suboptimal design of laboratory networks. The Global Health Security Agenda (GHSA) requires countries to establish a tiered national laboratory system and ?determine the level of diagnostic capability practical and needed at each level of the public health hierarchy from national to district.? Testing at lower tier laboratories improves turn-around time and can utilize simpler assays but adds costs and may sacrifice quality. By contrast, testing at higher tier laboratories may ensure better quality but requires transporting patient samples, with attendant delays and losses to follow-up. The optimal allocation of diagnostic resources is not obvious and decision makers must weigh many factors for multiple pathogens and available assays to establish a rational basis of a National Laboratory Strategic Plan. The overall objective of the proposed research is to identify the ideal placement of diagnostic testing for high priority infectious diseases in resource-limited countries, using Ghana as an example. To accomplish this objective, we will characterize the implementation, effectiveness, and efficiency of diagnosing key infectious diseases at different tiers and geographic/epidemiological settings within the Ghanaian public health laboratory network. We have selected a mix of three epidemic-prone diseases (EPDs: bacterial meningitis, yellow fever and measles) and three diseases of public health importance (DPHIs: HIV, tuberculosis and hepatitis C virus). We will seek to identify the optimal (i.e., most effective and most cost-effective, within a given affordability envelope) level of laboratory-based diagnostic testing for these 6 key infectious diseases as a function of disease progression, assay availability, and tiered system by developing a detailed suite of agent-based simulation models. As laboratory networks must function for all infectious diseases, a key innovation of our model is the integration of multiple conditions with different diagnostic testing algorithms, rather than focusing only on a single disease system. In Aim 1, we will collect empirical data on laboratory characteristics (e.g., tier, remoteness, test availability, testing delays, courier performance, costs), diagnostic effectiveness (estimated proportion of diagnoses that are both accurate and timely), and diagnostic efficiency (e.g., unit cost and cost per accurate/timely diagnosis). This will enable characterization of the current capacity and effectiveness of Ghana's public health laboratory network. In Aim 2, we will develop and integrate a streamlined set of simulation models that estimate relevant disease-specific outcomes for these priority EPD-DPHIs (e.g., number HIV-positive infants with timely ART initiation and unnecessary antibiotic prescriptions for meningitis averted).